Paet 1

Community MobilizationSeven Strategies to Affect Community Change Provide information Seminars/workshops2. Enhance skills As above3. Provide support Enable attendance 4. Enhance access/reduce barriers May be reversedChange consequences Reward positive and punish negative behaviors6. Change physical design Parks, lighting etc.7. Modify and change policies Laws and policies

U. of Kansas Work Group

Current TrendsEmerging Drug Items Identified in U.S. NFLIS Tox Labs: 2010 1/2 2012 (1/2 2012 incomplete)

SOURCE: U.S. DEA, Office of Diversion Control, NFLIS data, 2012.7This slide gives an indication of the number of items (e.g., seizures, samples, pills, powders, unknown substances) sent to toxicology laboratories across the U.S. that were identified as containing synthetic cannabinoids or synthetic cathinones. The National Forensic Laboratory System (NFLIS) organized by the Drug Enforcement Administration collects reports from most of the state and local police toxicology laboratories and from some medical examiners on the number of items of specific drugs identified in each laboratory. While the partial 2012 numbers are low, notice there were more cathinone items identified in the first half of 2012 than in all of 2011, whereas the number of synthetic cannabinoid items identified seems to be down. It is important to mention that the numbers of cannabinoid and cathinone items identified are low in comparison to illicit drugs. In 2011, there were 358,412 cannabis items identified and 228,376 cocaine items identified.

Additional Information for the Trainer(s)The DEA National Forensic Laboratory Information System (NFLIS) systematically collects results from drug chemistry analyses conducted by state and local forensic laboratories across the country. As a national drug forensic laboratory reporting system, NFLIS provides timely and detailed analytical results of drugs seized by law enforcement.It is a unique source of information for monitoring and understanding drug abuse and trafficking in the United States, including the diversion of legally manufactured drugs into illegal markets. Findings from NFLIS can also supplement existing drug data sources, including information from drug demand surveys and drug testing programs.

Over 300 state and local forensic laboratories in the United States perform nearly two million drug analyses each year. As of March 2012, 48 state laboratory systems and 91 local laboratory systems, representing 288 individual laboratories, are participating in NFLIS. In 2011, approximately 1.7 million drug analysis records were reported to NFLIS. This information is made available through semiannual, annual, and special reports. These reports include findings on major drug categories such as narcotic analgesics, depressants and tranquilizers, hallucinogens, anabolic steroids, and stimulants. They provide statistically representative national and regional drug item estimates for the most frequently identified drugs. National case estimates for the most frequently identified drugs are also presented.

NFLIS is one resource of information utilized by DEA to carry out its core mission. The NFLIS information system supports DEAs ability to track national, regional, and local drug patterns, including providing timely and geographically specific information on emerging drug problems.

7

Synthetic Drugs Will Turn You into a Zombie?

TRAINERS NAMETRAINING DATETRAINING LOCATION

The purpose of this educational training presentation is to provide clinicians from a variety of work and educational backgrounds (including, but not limited to physicians, dentists, nurses, other allied medical staff, therapists and social workers, counselors, specialists, and case managers working in substance use disorders, mental health, and other health-related settings) with a detailed overview of synthetic drugs, including substances known on the street as K2, Spice, and Bath Salts. The presentation defines key terms, describes the main classes of synthetic drugs commonly available, presents available data on the extent of use, provides information on identifying and assessing individuals who are using synthetic drugs, and concludes with some clinical implications of synthetic drug use. The duration of the presentation is approximately 1 -2 hours, depending on whether the presenter chooses to include all of the slides, or a selection of slides.

Slides 7-21 have been included for audiences who have little or no familiarity with psychoactive drugs and substance use disorder-related terminology. If you are presenting to an audience that is knowledgeable about substance use disorders, you may decide to hide these slides when presenting the rest of the information.

Case examples and clinical case studies have been inserted towards the conclusion of the presentation to encourage dialogue among attendees, and to illustrate how the information presented can be used clinically.Synthetic Cannabinoids: The Major Compounds

a) NaphthoylindolesJWH-018JWH-073JWH-398JWH-200JWH-081JWH-015JWH-122JWH-210JWH-019JWH-0075-Fluoropentyl-JWH-122b) Cyclohexylphenoles

CP-47,497-C8AM-2201JWH-020JWH-387AM-1220JWH-412

SOURCE: Agudelo et al. (2012). Effects of Synthetic Cannabinoids on the Blood Brain Barrier, Presented at 74th Annual CPDD.10Synthetic cannabinoid receptor agonists, often referred to as synthetic cannabinoids, are a large family of chemically unrelated structures functionally similar to 9-tetrahydrocannabinol (THC), the active principle of cannabis. Like THC, they bind to the same cannabinoid receptors in the brain and other organs as the endogenous ligand anandamide. They were developed over the past 40 years as potential pharmaceutical agents, often intended for pain management. However, it proved difficult to separate the desired properties from unwanted psychoactive effects (1).

This slide depicts two of the more common chemical structures, but so far, little is known about metabolism and toxicology of the synthetic cannabinoid compounds. It cannot be assumed that the risks associated with the use of synthetic cannabinoids will be necessarily comparable to those seen with THC, and indeed there are some reasons for concerns that these drugs may have a greater potential to cause harm. Because the synthetic cannabinoids in the Spice products have only been tested in the laboratory (in vitro or in animals), the health risk of the inhaled smoke is unknown. In the case of JWH-018, it can be speculated that, due to structural features, there may be a certain carcinogenic potential. Furthermore, accidental overdosing with a risk of severe psychiatric complications may be more likely to occur because the type and amount of cannabinoid may vary considerably from batch to batch even within the same product. In general, there may be a risk of the appearance of a full CB receptor agonist leading to life-threatening conditions if overdosed (unlike THC, which acts only as a partial agonist). What is clear is that further studies are needed to assess these risks reliably (2).

When tested, Spice has been found to contain over 250 artificial chemical compounds, including the ones above and new ones that we will talk about later. None of these chemicals are guaranteed safe for human consumption and the ingredients are not listed nor are instructions for use. Perhaps most worrisome: HU-210 has been found to be between 100 to 800 times more potent than THC, the main active chemical in marijuana (3).

REFERENCES:(1) Agudelo, M., Yndart, A., Morrison, M., Napuri, J., Samikkanu, T., Reddy, V.P., & Nair, M.P. (2012). Effects of Synthetic Cannabinoids on the Blood Brain Barrier. Presented at the 74th Annual College on Problems of Drug Dependence, La Quinta, California.(2) EMCDDA. (2009). Thematic paper Understanding the Spice phenomenon. Luxembourg: Office for Official Publications of the European Communities.(3) Devane, W.A. et al. (1992). A novel probe for the cannabinoid receptor. Journal of Medical Chemistry 35(11), 2065-2069.Synthetic Cathinones:Bath Salts

Could be MDPV, 4-MMC, mephedrone, or methyloneSold on-line with little info on ingredients, dosage, etc.Advertised as legal highs, legal meth, cocaine, or ecstasyTaken orally or by inhalingSerious side effects include tachycardia, hypertension, confusion or psychosis, nausea, convulsionsLabeled not for human consumption to get around laws prohibiting sales or possession

SOURCE: Wood & Dargan. (2012). Therapeutic Drug Monitoring, 34, 363-367.11Synthetic cathinones known as Bath Salts are one of the latest additions to a growing list of substances young people can use to get high. Bath Salts is a powder laced with a cocktail of chemicals that comes in either capsules or in loose form. A user can either swallow the capsule whole or use the powder, mixed with liquid, and injected. Sometimes it is snorted directly up the nose. It is said to replicate a cocaine or ecstasy high (1).

Synthetic cathinones are related to the parent compound cathinone, one of the psychoactive principals in khat. The synthetic powder is sold legally online and in drug paraphernalia stores under a variety of names, such as Ivory Wave, Purple Wave, Red Dove, Blue Silk, Zoom, Bloom, Cloud Nine, Ocean Snow, Lunar Wave, Vanilla Sky, White Lightning, Scarface, and Hurricane Charlie. Because these products are relatively new to the drug abuse scene, knowledge about their precise chemical composition and short- and long-term effects is limited, yet the known information warrants a proactive stance to understand and minimize any potential dangers to the publics health.

These products often contain various amphetamine-like chemicals, such as methylenedioxypyrovalerone (MPDV), mephedrone and pyrovalerone. These drugs are typically administered orally, by inhalation, or by injection, with the worst outcomes apparently associated with snorting or intravenous administration. Mephedrone is of particular concern because, according to the United Kingdom experience, it presents a high risk for overdose. These chemicals act in the brain like stimulant drugs (indeed they are sometimes touted as cocaine substitutes); thus they present a high abuse and addiction liability. Consistent with this notion, these products have been reported to trigger intense cravings not unlike those experienced by methamphetamine users, and clinical reports from other countries appear to corroborate their addictiveness. They can also confer a high risk for other medical adverse effects. Some of these may be linked to the fact that, beyond their known psychoactive ingredients, the contents of "bath salts" are largely unknown, which makes the practice of abusing them, by any route, that much more dangerous (2).

Additional Information for the Trainer(s)The list of synthetic cathinones is long: butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4- flouromethcathinone, methadone, mephedrone, methlenedioxypyrovalerone (MDPV), methylone and pyrovalerone, among others. Bupropion is the only cathinone derivative that has a medical indication in the U.S. and Europe. The first synthetic cathinone, methcathinone, was produced in 1928.

REFERENCES:(1) Wood, D.M. & Dargan, P.I. (2012). Use and acute toxicity associated with the novel psychoactive substances diphenylprolinol (D2PM) and desoxypipradrol (2-DPMP). Clinical Toxicology, 50, 727-732.(2) Volkow, N. (2011). Message from the Director: Bath Salts Emerging and Dangerous Products. Rockville, MD: National Institute on Drug Abuse.

11Bath salts

The number of calls to poison centers concerning "bath salts" rose from 304 in 2010 to 6,138 in 2011, according to the American Association of Poison Control Centers. More than 1,000 calls had been made in 2012 by June. [8]In addition to K2 and Spice, other street names include Black Mamba (Turnera diffusa), Bombay Blue, Fake Weed, Genie, and Zohai.[9] According to Partnership at Drugfree.org, other names also include Bliss, Blaze, JWH -018, -073, -250, Yucatan Fire, Skunk and Moon Rocks.[13]Designer DrugsSynthetic MarijuanaBath saltsis the informal "street name" for a family of designer drugs often containing substituted cathinones, which have effects similar to amphetamine and cocaine.[3][4][5] The white crystals resemble legal bathing products like epsom salts, and are called bath salts with the packaging often stating "not for human consumption" in an attempt to avoid the prohibition of drugs,[3] but chemically have nothing to do with actual bath salts.

Compared to THC, which is a partial agonist at CB1 receptors, JWH-018 (and many of its analogues) are full agonists. THC has been shown to inhibit GABA receptor neurotransmission in the brain via several pathways.[18][19] JWH-018 may cause intense anxiety, agitation, and, in rare cases (generally with non-regular JWH users), has been assumed to have been the cause of seizures and convulsions by inhibiting GABA neurotransmission more effectively than THC. Cannabinoid receptor full agonists may present serious dangers to the user when used to excess.[20]12What is DXM? Dextromethorphan is a psychoactive drug found in common over the counter cough medicines.

SOURCE: NIDA. (2001). NIDA Research Report Series: Hallucinogens and Dissociative Drugs. 13Jane Maxwell, UT UTATTC, 512 232-061013Dextromethorphan (DXM or Robo) is used to temporarily relieve cough caused by the common cold, the flu, or other conditions, when taken in high doses can produce effects similar to those of PCP and ketamine. Like PCP and ketamine, dextromethorphan acts as an NMDA receptor antagonist. The most common source of abused dextromethorphan is "extra-strength" cough syrup, which typically contains 3 milligrams of the drug per milliliter of syrup. At the doses recommended for treating coughs (1/6 to 1/3 ounce of medication, containing 15 mg to 30 mg dextromethorphan), the drug is safe and effective. At much higher doses (4 or more ounces) dextromethorphan produces dissociative effects similar to those of PCP and ketamine.

REFERENCE:NIDA. (2001). NIDA Research Report Series: Hallucinogens and Dissociative Drugs (printed March 2001). Rockville, MD: U.S. Department of Health and Human Services, National Institutes of Health.

14Monitoring the Future is an ongoing study of the behaviors, attitudes, and values of American secondary school students, college students, and young adults. Each year, a total of approximately 50,000 8th, 10th and 12th grade students are surveyed (12th graders since 1975, and 8th and 10th graders since 1991). In addition, annual follow-up questionnaires are mailed to a sample of each graduating class for a number of years after their initial participation. The Monitoring the Future Study has been funded under a series of investigator-initiated competing research grants from NIDA, a part of the National Institutes of Health. MTF is conducted at the Survey Research Center in the Institute for Social Research at the University of Michigan. Spice products are popular among adolescents and young adults. According to the 2011 Monitoring the Future survey, one in nine (11.4%) of high school seniors used Spice or K2 once over the past year, making synthetic marijuana the second most frequently used illicit drug, after marijuana, among high school seniors. Smaller percentages of respondents used MDMA, hallucinogens, or cocaine. Easy access and the misperception that Spice products are natural and therefore harmless have likely contributed to their popularity. In addition, the chemicals used in Spice are not easily detected in standard drug tests.14

Pain ManagementThe Risk-Benefit Framework:Judge the Treatment, not the PatientINAPPROPRIATE Is the patient good or bad?Does the patient deserve pain meds?Should this patient be punished or rewarded?Should I trust him/her?

APPROPRIATEDo the benefits of this treatment outweigh the untoward effects and risks in this patient or to society?17

Use a risk-benefit framework. It is important to judge the treatment, not the patient. Youre not asking: Is the patient good or bad?Does the patient deserve pain medications, namely opioids?Should the patient be punished or rewarded? Do I trust him or her?

Rather, the questions to ask are:

Do the benefits of this treatment, e.g., opioids, outweigh the untoward effects and risks to the patient or to society (including the concern of possible diversion)? What is the risk-benefit framework that needs to be kept in mind when deciding whether to begin opioids to treat chronic pain and over time when monitoring patientsare they benefiting or is there harm?

Daniel Alford, MD, MPH17What Is the Addiction Risk?Published rates of abuse and/or addiction in chronic pain populations are 3-19%1

Suggests that known risk factors for abuse or addiction in the general population would be good predictors for problematic prescription opioid use

Past cocaine use, history of alcohol or cannabis use2Lifetime history of substance use disorder3Family history of substance abuse, a history of legal problems and drug and alcohol abuse4Heavy tobacco use5History of severe depression or anxiety51 Fishbain et al. Clin J Pain, 1992; 2 Ives et al. BMC Health Services Research, 2006; 3 Reid et al. JGIM, 2002; 4 Michna el al. JPSM, 2004; 5Akbik H., et al. JPSM, 2006. 18Daniel Alford, MD, MPH18So what is the addiction risk of opioid use? Unfortunately, we dont really know. The published rates of abuse and addiction in chronic pain populations range between 3-19%.

Current literature suggests that risk factors for drug abuse in the general population may also apply to prescription drug abuse. These risk factors include: Heavy tobacco use Past use of alcohol, cannabis, and cocaineLifetime history of substance use disorderFamily history of substance abuse History of legal problemsHistory of severe depression and anxietyWhen Are Opioids Indicated?Pain is moderate to severe Pain has significant impact on functionPain has significant impact on quality of lifeNon-opioid pharmacotherapy has been tried and failedPatient agreeable to close monitoring of opioid use (e.g., pill counts, urine screens)19Daniel Alford, MD, MPH19When are opioids indicated? When pain is moderate to severe and has significant impact on function and on quality of life; When non-opioids have been tried and failed;

Importantly, when the patient is agreeable to close monitoring of opioids, which may include signing a controlled substance agreement and agreeing to pill counts and urine drug testing. Opioid Efficacy in Chronic PainPain relief modestSome statistically significant, others trend toward benefitOne meta-analysis decrease of 14 points on 100 point scaleLimited or no functional improvementMost literature surveys & uncontrolled case seriesRandomized clinical trials (RCTs) are short duration < 4 months with small sample sizes < 300 ptsMostly pharmaceutical-company sponsoredBalantyne JC, Mao, J. N Engl J Med, 2003.Martell et al. Ann Intern Med, 2007; Eisenberg et al. JAMA, 2005.20Daniel Alford, MD, MPH20What is the efficacy of long-term opioids in treating chronic pain? Overall, pain relief was modest in these studies. In one meta-analysis, the decrease of pain was 14 points on a 100 point scale. (Eisenberg et al. JAMA 2005.) So if your patient is expecting pain relief going from ten to zero with opioids, its very unlikely to happen. Better education is necessary regarding how effective opioids are and what is realistic in terms of pain relief goals. Also, and significantly, these studies show limited functional improvement, which is an important goal in pain management. The management of chronic pain is beyond the scope of this talk, but it is important for physicians and patients to realize that opioids ARE NOT a magic bullet and to understand the limitations of this therapy.

Most literature that studies opioids in chronic pain are surveys and uncontrolled case series. Randomized clinical trials are short in duration (less than 4 months) and involve small sample sizes (less than 300 patients). Most are pharmaceutical-company sponsored.

Opioid Dependence vs. Chronic Pain Managed with Opioids?The diagnosis of Opioid Dependence requires 3 or more criteria occurring over 12 months

Tolerance YESWithdrawal/physical dependence YESTaken in larger amounts or over longer periods MAYBEUnsuccessful efforts to cut down or control MAYBEGreat deal of time spent to obtain substance MAYBEImportant activities given up or reduced MAYBEContinued use despite harm MAYBE

American Psychiatric Association. DSM IV-TR, 2000.21Daniel Alford, MD, MPH21The diagnosis of OPIOID DEPENDENCE requires 3 or more of these criteria to occur over a 12 month period. However, many of these criteria may be present in a patient with chronic pain who is treated with chronic opioids. This may be due to poor pain control, the patients concern that the physician will not believe his or her pain and thus under-prescribe pain medications, etc.VeteransAlcohol Reported as Primary Substance of Abuse in 62% of Veterans Treatment AdmissionsCESARFAXU n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r kA Weekly FAX from the Center for Substance Abuse ResearchNovember 19, 2012Vol. 21, Issue 46

301-405-9770 (voice) 301-403-8342 (fax) CESAR@umd.edu www.cesar.umd.edu CESAR FAX may be copied without permission. Please cite CESAR as the source. SOURCES: Adapted by CESAR from Substance Abuse and Mental Health Data Archive (SAMHDA), online analysis of the concatenated1992-2010 Treatment Episode Data Set (TEDS), based on data received through 10/10/11, conducted 11/14/12 (available online at http://www.icpsr.umich.edu/icpsrweb/SAMHDA); andSubstance Abuse and Mental Health Services Administration (SAMHSA), Center for Behavioral Health Statistics and Quality, Half of Substance Abuse Treatment Admissions among Veterans Aged 21 to 39 Involve Alcohol as the Primary Substance of Abuse, Data Spotlight, November 8, 2012 (available online at www.samhsa.gov/data/2k12/TEDS2010N/TEDS2010NWeb.pdf).

*It is possible that veterans receiving treatment from VA treatment facilities may have a different pattern of primary substances of abuse than those found in TEDS.Primary Substance of Abuse in Treatment Admissions Ages 18 and Older, by Veteran Status, 2010(N=57,934)There were nearly 58,000 admissions of veterans to substance abuse treatment facilities in 2010, according to the most recent data from the Treatment Episode Data Set (TEDS). TEDS, a database of treatment admissions to primarily publicly-funded substance abuse treatment facilities, excludes admissions to Veterans Affairs (VA) facilities. Therefore, the veteran admissions in TEDS represent veterans who chose to seek substance abuse treatment in a non-VA facility.* While alcohol was most likely to be reported as the primary substance of abuse among veterans and nonveterans alike, veterans were much more likely than nonveterans to report alcohol as their primary substance of abuse (62% vs. 42%). Veterans were less likely than nonveterans to report marijuana (7% vs. 15%) or heroin (8% vs. 16%) as their primary substance of abuse. No other substance besides alcohol was reported by more than 10% of veterans as a primary substance of abuse, suggesting that use prevention, intervention, and treatment programs for military personnel and veterans should focus their resources on alcohol.

NOTES: A veteran is defined by TEDS as a person 16 years or over who has served (even for a short time), but is not now serving, on active duty in the US Army, Navy, Marine Corps, Coast Guard, or Commissioned Corps of the US Public Health Service or National Oceanic and Atmospheric Administration, or who served as a Merchant Marine seaman during World War II. Persons who served in the National Guard or Military Reserves are classified as veterans only if they were ever called or ordered to active duty, not counting the 4-6 months for initial training or yearly summer camps. More than two of ten Veterans with PTSD also have SUD. Almost one out of every three Veterans seeking treatment for SUD also has PTSD. In the wars in Iraq and Afghanistan, about one in ten returning soldiers seen in VA have a problem with alcohol or other drugs. New research from the University of Michigan suggests that veterans battling post-traumatic stress (PTSD) and substance abuse disorders face a greater risk of death.Veterans, PTSD, and Substance Use Disorders

Primary Substance of Abuse in Treatment Admissions Aged 21 to 39, by Veteran Status: 2010 Percent 40 20 60 50 30 10 0 50.7 34.4 Alcohol 9.0 Heroin Other Opiates 16.8 1 7.6 12.2 12.0 12.2 Marijuana Meth- amphetamine Crack 6.2 7.6 6.3 7.2 Veterans Nonveterans Cocaine/ http://www.healthquality.va.gov/Substance_Use_Disorder_SUD.asp

The guideline describes the critical decision points in the Management of Substance Use Disorder and provides clear and comprehensive evidence based recommendations incorporating current information and practices for practitioners throughout the DoD and VA Health Care systems. The guideline is intended to improve patient outcomes and local management of patients with substance use disorder.

Where to Go from HereThe guideline is formatted as five algorithms, with annotations: Algorithm A- Screening and Initial Assessment for Substance Use Disorder Algorithm B- Management of SUD in Specialty SUD Care Algorithm C- Management of SUD in (Primary) General Healthcare Algorithm P- Addiction-Focused Pharmacotherapy Algorithm S- Stabilization and Withdrawal Management

Chart12072140568708267371303

201020111/2 20122,07214,0568,7081,303

Sheet1Synthetic CannabinoidsSynthetic Cathenones20102072262011140567371/2 201287081303To resize chart data range, drag lower right corner of range.